Hypoxia-inducible Factor-1α Suppression in Ovarian Clear-cell Carcinoma Cells by Silibinin Administration.

Abstract

BACKGROUND/AIM:

Advanced ovarian clear-cell carcinoma (CCC) fails to respond to standard chemotherapy, and has a poor prognosis. Since hypoxia-inducible factor-1 (HIF-1) stimulates various genes involved in cancer, we aimed to examine the efficacy of silibinin, an active component of milk thistle belonging to Asteraceae, in suppressing HIF-1 activity, and elucidate the underlying mechanism in human CCC cell lines.

MATERIALS AND METHODS:

Human ovarian CCC cell lines HAC-2, OVISE, and RMG-1 were treated with 500 μM silibinin for 4 h under normoxic and hypoxic conditions. Using DNA microarray, we analysed genes whose expression modulated more than 2-fold in response to hypoxia, whereas HIF-1α expression was measured using ELISA.

RESULTS:

Silibinin treatment decreased HIF-1α protein in all cell lines, and eIF4E2 and RPS6 mRNA in HAC-2 and RMG-1 cells.

CONCLUSION:

Silibinin suppressed HIF-1α protein under hypoxic conditions in CCC cell lines and could be a potential anti-cancer drug.

• Authors: Mariko Miyazawa, Masanori Yasuda, Masaki Miyazawa, Naoki Ogane, Tomomi Katoh, Mitsutake Yano, Takeshi Hirasawa, Mikio Mikami, Hitoshi Ishimoto
• Journal: Anticancer research (Anticancer Res) Vol. 40 Issue 12 Pg. 6791-6798 (Dec 2020) ISSN: 1791-7530 [Electronic] Greece
• PMID: 33288572 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Biomarkers
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Silybin
• L-Lactate Dehydrogenase

Topics

• Adenocarcinoma, Clear Cell (drug therapy, genetics, metabolism)
• Antineoplastic Agents, Phytogenic (administration & dosage)
• Biomarkers
• Cell Hypoxia
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (antagonists & inhibitors, metabolism)
• L-Lactate Dehydrogenase (metabolism)
• Ovarian Neoplasms (drug therapy, genetics, metabolism)
• Signal Transduction (drug effects)
• Silybin (administration & dosage)